Tag Archives: biology

Scientists, like most people, want to understand the world they live in. We examine the physical structure of the world, in the hope that understanding the rules governing it will also lend some clue as to what it all means. Ironically, as the boundaries of scientific knowledge grow, the possibility of any individual scientist grasping this entire meaning gets smaller and smaller. Even within science, the traditional disciplinary boundaries—biology, chemistry, physics—often separate scientists who should really be talking to each other. I have always loved talking to people who know different things than I do, prompted by curiosity and encouraged by family. But it can be rare to see famous scientists doing the same.

Erwin Schrödinger, a physicist famous for his mathematical and philosophical development of quantum mechanics, tried to reach across these boundaries and ask the question that compels so many of us, namely ‘What Is Life?’ His historic lectures were given in 1943, against the backdrop of world war and 75 years behind our current understanding of biology. And in a wise move for anyone trying to understand something new, Schrödinger began by admitting what he didn’t know: to him, the difference between what physics and biology had to say about life was the difference between “a wallpaper and a Raphael tapestry”.

And yet, connecting physical understanding to biology has provided significant insights. When these lectures were given, the DNA molecule itself had already been discovered, but the double helix structure was yet to be found, along with much of our modern understanding of how this blueprint for life works. And yet the stability of the DNA molecule in the cell is directly due to the quantum basis of chemical bonds. Schrödinger expresses amazement that even with the perturbations caused by heat and environment at the molecular level, the naive physicist’s expectation of wild variability is incorrect, and chemical stability holds. While DNA does sometimes mutate in ways that persist through generations, forming the basis of natural selection, its ability to reproduce error free throughout our lives is amazing from a physics perspective. Especially when one considers the consequences of uncontrolled mutation, as the world would see only two years later as radiation-induced mutation caused terrible illness in the survivors of Hiroshima and Nagasaki.

In trying to define life, Schrödinger comes to the idea of order and disorder, and the physicist’s idea of entropy. Although entropy, which is a measure of disorder, is bound to increase over time subject to the Second Law of Thermodynamics, Schrodinger posited that living beings were effectively decreasing their local entropy by exporting it, increasing order within the cell even if the broader environment became less ordered. Cheating the Second Law of Thermodynamics is a necessity for living cells, living beings, and even our planet to maintain local order. Schrodinger then concludes that living beings must be ‘negative entropy machines’, converting energy to local order, a perspective only a physicist could have come up with.

Schrödinger’s willingness to admit what he did not know, and try to combine modern biology and modern physics even during wartime to unify humanity in knowledge, put me in mind of another, less famous, transdisciplinary scientist.

My father, Eric Fairfield, was a biochemistry professor who left academia to work on the Human Genome Project. We talked about science a lot, especially once I chose to pursue physics. I know he was proud of me for becoming a scientist, even though as a biochemist he could not resist ribbing me for my limited understanding of biology. When I read Schrodinger’s statement:

THE CLASSICAL PHYSICIST’S EXPECTATION, FAR FROM BEING TRIVIAL, IS WRONG

I could nearly hear it in my dad’s voice. The “naive physicist’s approach” to understand the cell by looking to statistical physics and randomnessi misses the stability of chemical bonds in the DNA molecule and other cellular components. In a messy, changeable environment, the blueprints that make us have persisted through thousands of generations. As my dad used to say, biology had this figured out a long time before we even knew what questions to ask.

But this isn’t to say that physicists have no business asking questions in biology, or vice versa. Biology is built on the laws of physics and chemistry, even if the exact details of how are still being puzzled out today. And questions that my dad put to me, as part of his own research, often had me questioning both physics and biology. How does a cell know what organ to build a piece of? What biochemical signals lead to the evolution of our own sensory organs, like ears or eyes? How does higher level order arise from molecule level decisions?

I enjoyed discussing these questions with him, and asking my own about the chemistry of the nanomaterials I studied, and their current and possible future biological applications. But the last big biological questions my dad asked ended up being about cancer, a scientific issue that has absorbed the careers of many researchers. Colon cancer took my father’s life last year, and when I have a question about biology, I can no longer call him to see if he’s thought about it before. At his memorial service, many friends commented how much they enjoyed talking science with my dad, whether they had a scientific background or not. He enjoyed discussing and debating these topics with anyone, even if and sometimes especially if they had a vastly different perspective to his own. But I think science would get a little bit further if we had more scientists like my father, or like Erwin Schrödinger, who were willing to cross disciplinary boundaries, admit what they don’t know, and see where they can go from here.

My scientific colleagues may find this to be a very personal response to a scientific matter. But Schrödinger himself dedicated What Is Life? to the memory of his parents. We are all searching for answers together, inspired by those who have come before, and certain to be surprised by what comes next.

One of the most exciting things about working in nanoscience is the incredible level of precision with which we can probe the world around us. This includes not just the physical world but also the biological world, which is a lot messier than most physicists are comfortable with!

There is currently intense interest in sequencing DNA via translocation through a nanopore, like threading a needle with the molecule that contains instructions for building life. Protein nanopores are the basis of new technology for DNA sequencing that made the news recently, costing only $1000 for full DNA sequencing with a palm-sized device from Oxford Nanopore. The protein nanopore is pictured in the image below, with DNA unspooling to pass through the pore.

But these nanopores can also be created in silicon, graphene or other thin materials. These solid state nanopores emulate the very small biological pores which can be found in the lipid bilayer around cells and their nuclei. Macroelectrodes in solution on either side of a solid state nanopore drive an ionic current in the carrier solution through the nanopore. As the DNA passes through the nanopore, it physically blocks the ionic current through the nanopore, allowing detection of translocation events. Additional electrodes can be added across the nanopore to enhance sensitivity to DNA. While research in this area is ongoing, it is thought that noise in the electrical signal through the nanopore can eventually be lowered—by applying coatings, slowing translocation speeds and improving fabrication techniques—to enable base pair sensitivity for DNA sequencing. Using solid state nanopores for sequencing could lead to more reliability and lower costs than protein sequencing, and is a major research area of the Drndić group at UPenn, the group I worked in for my PhD!

To me, nanopore sequencing is an amazing example of how direct electrical interaction with nanostructures can yield important information about not just the world around us, but our own place in it.

Recently something unusual happened: I had an idea that was illustrated and published in Wired. They have a gallery of hybrid animals up, including drawings made by students in the CSU Monterey Bay Science Illustration Program, and my contribution was bioluminescent starlings. I personally think that watching a murmuration of glowing starlings flocking would be amazing. But how does bioluminescence work exactly?

Bioluminescence is light emission from a living creature. How does that happen? Remember that light is a form of energy, and if a particle undergoes a transition from one energy level to another, the difference in energy has to go somewhere and may be emitted as light. Much of the light we get from the sun comes from atomic energy level transitions that happen inside it. But the same thing can also occur in more complex chemical reactions: excess energy can be used to create a new compound, or heat up the reactants, but it may also be emitted as light. (Whether or not this happens depends on the mechanism of the chemical reactions and, as usual, on energy minimization.)

So bioluminescence occurs when a chemical reaction happens, inside a living organism, that emits light. It’s actually relatively common in deep-sea creatures, who don’t have much other light around. But it’s also seen closer to shore in bioluminescent algae, and on dry land with fireflies. What these creatures have in common is that they produce luciferin, a class of pigments that can be oxidized to produce light, and luciferase, an enzyme that catalyzes the reaction. These creatures can then use the bioluminescence to communicate with other creatures, for camouflage, luring prey, or attracting mates.

Some plants show bioluminescence too, though there are many competing theories on whether they gain some evolutionary advantage from it or not. But there are also many researchers working to introduce bioluminescence into plants and animals, by adding the genes that create luciferin and luciferase, or by adjusting their expression. Self-lighting could help with imaging, but making more things bioluminescent has both a practical and an aesthetic appeal.

Entropy is a measure of how many configurations could yield the same macrostate, and thus how probable the macrostate is. It can be a measure of information, or a measure of disorder in a physical system. But what about the entropy of biological systems?

Relatively few configurations yield life, compared to the many that don’t. Life is highly ordered, so living organisms should have much lower entropy than their non-living constituents. In fact, using energy to create and maintain order is one of the key signatures of life! One implication of life having low entropy is that life is improbable, which so far seems to be true based on the limited observations we have of other planets. But another implication is that living things act to reduce entropy locally, in the organism, there must be a corresponding increase in entropy somewhere else to offset that reduction. This is required because of the second law of thermodynamics, which says that by far the most statistically probable outcome is an entropy increase. But the second law applies to ‘closed systems’, which means a system that cannot exchange heat or energy with its surroundings. An organism that can interact with its surroundings can expel entropy via heat, to gain local order and reduce local entropy. Global disorder still increases, but for that organism, the ability to locally reduce entropy is literally a matter of life and death.

An obvious example of this principle is humans. Our human bodies are very highly ordered compared to inanimate things like air and water. Even compared to dirt, which has a whole ecosystem of microbiota and larger organisms like worms, a human represents many times more order. But this doesn’t contradict the second law, because the way we maintain life is to take in food and expel very disordered waste products. Humans can extract the chemical energy in the food and use it to maintain or decrease local entropy levels, and thus stay alive. Obviously other animals do this too, though they may eat different things than we do or digest them in different ways. And actually, the plants that we and other animals eat have done something similar, except that instead of getting chemical energy from combustion they are able to extract it directly from the sun’s light. Plants maintain their low entropy by releasing heat and high-entropy waste products, and anything that eats plants (or that eats something that eats plants) is converting solar energy into local order as well as expelled heat.

If you’re really feeling clever, you might ask, what about the planet Earth? If we’re receiving all this sunlight, and making life from it, shouldn’t there be a corresponding buildup of entropy on the planet, in the form of waste heat or some other disordering? Isn’t the Earth a closed system, isolated in space, whose order is constantly increasing?

But if a closed system is one which exchanges no heat with its surroundings, then the Earth doesn’t qualify because it is obviously exchanging heat with the Sun! The Earth receives a massive number of photons from the sun, which is where plants, and by extension the rest of us, get energy to create order. But in addition, the Earth is also radiating energy and heat into space, as all objects do. The incident energy from the sun is directional, high-energy, and highly ordered, but the energy the Earth radiates into space is in all directions, low-energy, and very disordered. That’s where the excess entropy is going!

Thus, life on our dear planet is not a violation of the second law of thermodynamics at all, because living organisms and even huge ecosystems are not closed systems. What’s more, the creation of order from chaos actually requires a net increase in entropy: it requires a reconfiguration of atoms and microstates, and the most likely outcome of any reconfiguration is an increase in entropy. Many of chemical reactions necessary for life are entropically driven, where the outcome has many more available states than the inputs so the reaction is statistically favored to occur. Organisms that do work to create order must also create entropy, and the organisms most likely to survive are often those with the most clever control of entropy generation. So the proliferation of life is not threatened by entropy, as in the popular conception, but actually depends on entropy generation!

In our exploration of electronics, we started at the atomic level with the fundamental properties of subatomic particles. We looked at emergent properties of collections of atoms, like the origins of chemical bonding and electronic behavior of materials. Recently we have started to move up in scale, seeing that individualcircuitcomponents affect the flow and storage of electrons in different ways. At this point I think it is worthwhile to take a step back and look at the larger picture. While individual electrons are governed by local interactions that minimize energy, we can figure out global rules for a circuit component that tell us how collections of electrons are affected by a resistor or some other building block, creating the macroscopic quantity we call current. From there we can create collections of circuit components that perform various operations on the current passing through them. These operations can again be combined, and where we may have started with a simple switch, we can end up with a computer or a display or a control circuit.

One way to picture it is like a complex canal system for water: we have a resource whose movement we want to manipulate, to extract physical work and perhaps perform calculations. At a small scale, we can inject dye into a bit of water and watch its progress through the system as it responds to local forces. But we can look at water currents at a larger scale by adding up the behavior of many small amounts of water. In fact, scale is a type of context, a lens through which a system can look quite different! Electrical engineers who design complex circuits for a living tend to work at a much higher level of abstraction than do scientists working on experimental electronic devices. The electrical engineers have to be able to imagine and simulate the function of impressive numbers of transistors, resistors, and other components, as shown below. Whereas a device physicist focuses on the detailed physics in a single circuit component, to learn what its best use might be. They are each working with the same system, but in different and complementary ways.

When I first started writing here, I talked about science as a lens through which we can view the world: a set of perspectives that let us see the things around us in a different way than we are used to. But there are lots of different worldviews and perspectives within science, depending on scale as well as other contexts. A discussion of electrical current, for example, could be handled quite differently depending on whether electrons are moving through a polar solvent like water, or synapses in the brain, or a metal wire connecting a capacitor to an inductor. Scientists who have trained in different fields like physics, chemistry, or biology can imagine very different contexts for discussions of the same phenomenon, so that even when the fundamental science is the same, the narrative and implications may change between contexts.

But in the end, whether you are a scientist or just interested in science, it helps to know not only that an electron is a tiny charged particle, but also how it behaves in electronic circuits, in chemical bonds between atoms, and in biological systems. And to know that it’s possible to build computers out of gears, billiard balls, or even crabs! But the size and properties of electronic computers have led them to dominate, at least for now.